Epigenetic mechanisms of TNFα activation in patients with cancer endometry

An important aspect of the management of patients with endometrial cancer (ER) is the timely identification of risk groups, early signs of the onset and recurrence of the disease. There is an active search for new markers for early diagnosis, detection of relapses and postoperative monitoring of RE. Tumor necrosis factor alpha (TNFα) is a cytokine involved in the pathogenesis of various forms of cancer, as well as associated with chronic inflammation, obesity. The goal is to study the methylation of the TNFa gene in the OM and the possibility of using it as a marker for forecasting, monitoring, and the risk of developing the OM. Materials and methods. DNA methylation was determined by the method of pyrosequencing in endometrial specimens taken from 10 patients with verified endometrial hyperplasia and 13 patients with RE when performing hysteroscopy with endometrial biopsy or endometrial curettage. Results and discussion. The total degree of methylation of the TNFα gene DNA promoter in the samples under study in patients with simple and / or complex nonatypical endometrial hyperplasia was 62.6 ± 12.8% and was higher than in RE patients (34.7 ± 8.8%). Findings. The results of the study showed the involvement of the epigenetic mechanism, which is associated with hypomethylation of the TNFα gene promoter, which can lead to the activation of the TNFα gene in RE. Determining the amount of methylation DNA promoter of the TNFα gene can be used as a potential prognostic and diagnostic marker for ER

Epigenetic mechanisms of TNFα activation in patients with endometrial cancer

Timely identification of risk groups, early signs of the disease onset and recurrence is an important aspect in management of endometrial cancer (EC) patients. There is an active search for early diagnosis new markers, detection of relapses and EC postoperative monitoring. Tumor necrosis factor alpha (TNFα) is a cytokine involved in the pathogenesis of various forms of cancer, as well as associated with chronic inflammation, obesity. The objective is to study TNFa gene methylation in EC and the possibility of its use as a marker for forecasting, monitoring, and EC risk development. Materials and methods. DNA methylation was determined by pyrosequencing in endometrial specimens taken from 10 patients with verified endometrial hyperplasia and 13 patients with EC when performing hysteroscopy with endometrial biopsy or endometrial curettage. Results and discussion. The total degree of methylation of the TNFα gene DNA promoter in the samples under study in the patients with simple and / or complex nonatypical endometrial hyperplasia was 62.6 ± 12.8%, which is higher than in EC patients (34.7 ± 8.8%). Conclusions. The results obtained showed the involvement of epigenetic mechanism associated with hypomethylation of the TNFα gene promoter, which can lead to the activation of the TNFα gene in EC. Determination of methylation DNA promoter of the TNFα gene and its amount can be used as a potential prognostic and diagnostic marker of EC

Половые отличия пула свободных аминокислот-нейромедиаторов у крыс Крушинского-Молодкиной

The study of the role of neurotransmitter systems in the pathogenesis of epilepsy is one of the priorities of epileptology. New data on the functions of free neurotransmitter-like amino acid in the central nervous system are of the greatest importance and determine the prospects for the development of novel effective anticonvulsants. It is widely believed in clinical medicine that epilepsy has distinct gender characteristics. The aim of this study was to investigate the gender peculiarities in the content of neurotransmitter amino acids in the brain of Krushinsky-Molodkina (KM) rats, which were used as model organisms for the study of genetically induced audiogenic epilepsy. The content of Asp, Glu, GABA, Gly, and Tau of the medulla oblongata, hippocampus and cerebral cortex were determined using high-performance liquid chromatography (HPLC) in intact KM rats, KM rats exposed to a series of epileptiform seizures, and Wistar rats (control group). Both the Wistar and KM rats had gender distinctions in the distribution of free amino acids among the investigated brain parts. The audiogenic epilepsy was characterized by smoothing gender differences as well as differences between the concentrations of free amino acids in the cortex and medulla oblongata, specific for Wistar rats. The changes observed in male rats after the set of seizures included the increase in GABA concentration and a decrease in the Gly level in all investigated brain parts, as well as the decrease of the Tau content in the cortex and hippocampus. At the same time, the Glu content in cortex increased, while the Asp level decreased. After 6 days of audiogenic stimulations the female KM rats demonstrated the increase in the Glu level in all investigated brain parts, the increase in Gly and Asp levels in hippocampus, and no changes in the GABA content. Thus, after the set of epileptiform seizures the KM rats achieved a new steady state of the studied amino acids pool, which differed in males and females. In this case, gender differences significantly changed after the seizures. © 2020 Russian Academy of Medical Sciences. All rights reserved.The work was performed within the framework of the state task of the IIF UB RAS (Registration number AAAA-A18-118020590108-7)

Solid-state synthesis and characterization of ferromagnetic Mn5Ge3 nanoclusters in GeO/Mn thin films

Mn5Ge3 films are promising materials for spintronic applications due to their high spin polarization and a Curie temperature above room temperature. However, non-magnetic elements such as oxygen, carbon and nitrogen may unpredictably change the structural and magnetic properties of Mn5Ge3 films. Here, we use the solid-state reaction between Mn and GeO thin films to describe the synthesis and the structural and magnetic characterization of Mn5Ge3(Mn5Ge3Oy)-GeO2(GeOx) nanocomposite materials. Our results show that the synthesis of these nanocomposites starts at 180°С when the GeO decomposes into elemental germanium and oxygen and the resulting Ge atoms immediately migrate into the Mn layer to form ferromagnetic Mn5Ge3 nanoclusters. At the same time the oxygen atoms take part in the synthesis of GeOx and GeO2 oxides and also migrate into the Mn5Ge3 lattice to form Mn5Ge3Oy Nowotny nanoclusters. Magnetic analysis assumes the general nature of the Curie temperature increase in carbon-doped Mn5Ge3Cx and Mn5Ge3Oy films. Our findings prove that not only carbon, but oxygen may contribute to the increase of the saturation magnetization and Curie temperature of Mn5Ge3-based nanostructures

Assessment of the risk factors of the development of complex atypical endometrial hyperplasia in women

Проведен ретроспективный анализ анамнестических данных у 42 пациенток с патоморфологически подтвержденным диагнозом комплексной атипической гиперплазии эндометрия в возрасте 29–67 лет и у 30 женщин контрольной группы без верифицированного гиперпролиферативного процесса эндометрия (ГПЭ). Оценка полученных результатов путем вычисления отношения шансов факторов риска показало наличие статистически значимых и статистически незначимых факторов. С целью своевременного повышения мер профилактики, ранней диагностики ГПЭ необходимо выявлять факторы риска на догоспитальном этапе (в поликлиниках, женских консультациях, амбулаториях семейного врача) и проводить их коррекцию.Hyperproliferative processes of endometrium (HPE) in modern gynecology are considered as a polyethiological disease, which is influenced by various endogenous and epigenetic factors for development, progression and transformation. Endometrial hyperplasia, in combination with concomitant gynecological and extragenital pathology, increases the risk of developing uterine cancer in these patients. Aim. To determine and evaluate the most important risk factors for the development of complex atypical endometrial hyperplasia in women of reproductive and perimenopausal age. Materials and methods. A retrospective analysis of anamnestic data was performed in 42 patients with a pathologically confirmed diagnosis of complex atypical endometrial hyperplasia at the age of 29–67 years and in 30 women in the control group without verified HPE. Research results. The most significant risk factor for complex atypical endometrial hyperplasia development is age > 50 years (OR=119.89; 95% CI 6.83–2104.31); Heredity — OR= =80.78 (95% CI 4.63–1409.13). For patients with early menarche and late menopause, OR is 31.9 (95% CI 3.97–256.22) and 66.95 (95% CI 3.84–1166.55) respectively. Relatively high risk of complex atypical endometrial hyperplasia is associated with thyroid diseases — OR=27.91 (95% CI 1.58– 491.23), obesity OR=18.66 (95% CI 3.925–88.77), arterial hypertension OR=14.00 (95% CI 2.95– 66.41). Conclusions. In order to timely increase the prevention, early diagnosis of HPE, it is necessary to identify their risk factors at the prehospital stage and to correct them

Антивирусная и интерферониндуцирующая активность новых соединений – производных индолхиноксалинов

Проблематика. Розробка нових препаратів з антивірусною активністю та здатністю індукувати інтерферон є актуальним завданням з огляду на стрімке поширення вірусних інфекцій, формування резистентних до існуючих антивірусних препаратів штамів вірусів, загальне зниження імунної відповіді. Мета дослідження. Визначення антивірусної та інтерфероногенної активності похідних індолохіноксалінів в умовах in vitro. Методика реалізації. У роботі в умовах in vitro на перещеплюваній культурі клітин ST вивчали антивірусну та інтерфероніндукуючу дію 18 нових новосинтезованих сполук – похідних індолохіноксалінів. Результати дослідження. Показано здатність досліджуваних речовин пригнічувати розвиток вірусного цитопатичного ефекту на моделі ST-BBC тільки при лікувальній схемі введення. На моделі перещеплюваних культур клітин ST показано, що 12 із 18 досліджених сполук у концентраціях 0,1–0,2 мкг/мл здатні до індукції ІФН. Висновки. Серед досліджених сполук – похідних індолохіноксаліну як перспективну для подальших досліджень визначено сполуку RG-61, яка проявляє низьку токсичність (порівняно зі сполуками низки похідних) і антивірусну активність у інфікованих клітинах, а також здатна до індукції ІФН.Background. The development of new drugs with antiviral activity and the ability to induce interferon is an urgent task, taking into account the rapid spread of viral infections, development of resistance the virus strains to existing antiviral drugs and the overall decline of the immune response. Objective. Determine the antiviral activity and interferon inducer actions of indolequinoxalines derivatives in terms of in vitro. Methods. The work on PST cell cultures in conditions of in vitro antiviral and interferon inducer of the 18 new indolequinoxalines derivatives was studied. Results. The ability of indolequinoxalines derivatives to inhibit the development of viral cytopathic effect on the model PST-BBC only in therapeutic regimens was shown. In the model of inoculated cell cultures PST is shown that 12 compounds are capable of inducing interferon in low concentrations. Conclusions. Among the indolequinoxalines derivatives RG-61 compound as a promising for further studies was identified, which has a low toxicity (as compared to a number of compounds derived), has antiviral activity in infected cells and is capable of inducing IFN.Проблематика. Разработка новых препаратов с антивирусной активностью и способностью индуцировать интерферон является актуальной задачей с учетом стремительного распространения вирусных инфекций, формирования резистентных к существующим антивирусным препаратам штаммов вирусов, общего снижения иммунного ответа. Цель исследования. Определение антивирусной и интерфероногенной активности производных индолохиноксалинов в условиях in vitro. Методика реализации. В работе на культурах клеток ST в условиях in vitro изучали противовирусное и интерферониндуцирующее действие 18 новых новосинтезированных соединений – производных индолохиноксалинов Результаты исследования. Показана способность исследуемых веществ подавлять развитие вирусного цитопатического эффекта на модели ST-BBC только при лечебной схеме введения. На модели перевиваемых культур клеток ST показано, что 12 из 18 исследованных соединений вызывают индукцию ИФН в достаточно низких концентрациях. Выводы. Среди исследованных соединений производных индолохиноксалина как перспективное для дальнейших исследований определено соединение RG-61, которое проявляет низкую токсичность (по сравнению с соединениями ряда производных) и антивирусную активность в инфицированных клетках, а также индуцирует ИФН